Post-operative Dental Pain Study Comparing Two Different Dosage of Analgesic Efficacy

• ClinicalTrials.gov Identifier: NCT01075243
• Recruitment Status: Completed
• First Posted: February 25, 2010
• Results First Posted: April 29, 2015
• Last Update Posted: April 29, 2015
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: February 23, 2010
• First Posted Date: February 25, 2010
• Results First Submitted Date: June 20, 2013
• Results First Posted Date: April 29, 2015
• Last Update Posted Date: April 29, 2015
• Study Start Date: November 2009
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2015)

Sum of Pain Relief and Pain Intensity Differences From 0 to 6 Hours (SPRID 6 Hours) [ Time Frame: Every two hours from Baseline to 6 hours post dose ]

SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -5.8 (least pain relief) to 40.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline [pain severity score range:0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain using a 4-point categorical Verbal Rating Scale (VRS)]. If the subject rated pain intensity as 2 or 3, pain was assessed using a 100 mm Visual Analog Scale (VAS) [0 (no pain), 100 (worst pain)]. VAS scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale [0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief]

• Original Primary Outcome Measures (submitted: February 23, 2010): Change from baseline in the Sum of Pain Relief and Pain Intensity Differences (SPRID) at 6 hours [ Time Frame: Baseline to 6 horus post dose ]

Current Secondary Outcome Measures (submitted: April 27, 2015)

• Time to Confirmed First Perceptible Relief [ Time Frame: Baseline to 6 hours post dose ]
  Participants recorded the time to first perceptible relief by starting the first stopwatch at the time of dosing and stopping it when he/she experienced the first perceptible pain relief. The first perceptible pain relief was confirmed if the participant also stopped the second stopwatch indicating meaningful relief.
• Time to Onset of Meaningful Pain Relief [ Time Frame: Baseline to 6 hours post dose ]
  Participants recorded the time to meaningful relief by stopping a second stopwatch when they first began to experience meaningful relief.
• Time to Start Using Rescue Medication [ Time Frame: Baseline to 6 hours post dose ]
  Median time of use of rescue medication by participants.
• Percentage of Participants Who Took Rescue Medication at 2 Hours [ Time Frame: Baseline to 2 hours post dose ]
  Percentage of participants who received rescue medication at different time points post dose.
• Percentage of Participants Who Took Rescue Medication at 6 Hours [ Time Frame: Baseline to 6 hours post dose ]
  Percentage of participants who received rescue medication at different time points post dose.
• SPRID at 2 Hours [ Time Frame: Every two hours from baseline to 2 hours post dose ]
  SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -1.8 (least pain relief) to 12.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline [pain severity score range:0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain using a 4-point categorical Verbal Rating Scale (VRS)]. If the subject rated pain intensity as 2 or 3, pain was assessed using a 100 mm Visual Analog Scale (VAS) [0 (no pain), 100 (worst pain)]. VAS scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale [0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief
• SPRID at 4 Hours [ Time Frame: Every two hours from baseline to 4 hours post dose ]
  SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -3.8 (least pain relief) to 26.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline [pain severity score range:0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain using a 4-point categorical Verbal Rating Scale (VRS)]. If the subject rated pain intensity as 2 or 3, pain was assessed using a 100 mm Visual Analog Scale (VAS) [0 (no pain), 100 (worst pain)]. VAS scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale [0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief
• Total Pain Relief Score (TOTPAR) at 2 Hours [ Time Frame: Every two hours from baseline to 2 hours post dose ]
  TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120. Higher score indicated greater pain relief. TOTPARt = ∑PR x (timet - timet-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale [0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief].
• TOTPAR at 4 Hours [ Time Frame: Every two hours from baseline to 4 hours post dose ]
  TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240. Higher score indicated greater pain relief. TOTPARt = ∑PR x (timet - timet-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale [0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief].
• TOTPAR at 6 Hours [ Time Frame: Every two hours from baseline to 6 hours post dose ]
  TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240, 240-300 and 300-360. Higher score indicated greater pain relief. TOTPARt = ∑PR x (timet - timet-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale [0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief].
• Sum of Pain Intensity Difference (SPID) Scores at 2 Hours [ Time Frame: Every two hours from baseline to 2 hours post dose ]
  SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (timet - timet-1) Pain Intensity was assessed at baseline and at each time-point based on a 4-point categorical Verbal Rating Scale (VRS) scale: 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain. If the subject rated pain intensity as "2" or "3", pain was assessed using a 100 mm Visual Analog Scale (VAS) [0 (no pain), 100 (worst pain)]. VAS scores were converted into PID scores by subtracting them from pain scores taken at baseline.
• SPID Scores at 4 Hours [ Time Frame: Every two hours from baseline to 4 hours post dose ]
  SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (timet - timet-1) Pain Intensity was assessed at baseline and at each time-point based on a 4-point categorical Verbal Rating Scale (VRS) scale: 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain. If the subject rated pain intensity as "2" or "3", pain was assessed using a 100 mm Visual Analog Scale (VAS) [0 (no pain), 100 (worst pain)]. VAS scores were converted into PID scores by subtracting them from pain scores taken at baseline.
• SPID Scores at 6 Hours [ Time Frame: Every two hours from baseline to 6 hours post dose ]
  SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0-15, 15-30, 30-45, 45-60, 60-90, 90-120, 120-240, 240-300 and 300-360. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (timet - timet-1) Pain Intensity was assessed at baseline and at each time-point based on a 4-point categorical Verbal Rating Scale (VRS) scale: 0-no pain, 1-mild pain, 2-moderate pain, 3-severe pain. If the subject rated pain intensity as "2" or "3", pain was assessed using a 100 mm Visual Analog Scale (VAS) [0 (no pain), 100 (worst pain)]. VAS scores were converted into PID scores by subtracting them from pain scores taken at baseline.
• Participants Global Assessment to Response to Treatment (PGART) [ Time Frame: Baseline to 6 hours post dose ]
  PGART was measured by a score in a scale from 0-4: 0- Poor; 1- Fair 2- Good; 3- Very Good; 4- Excellent.

Original Secondary Outcome Measures (submitted: February 23, 2010)

• Time to meaningful relief [ Time Frame: Baseline to 6 hours post dose ]
• Proportion of subjects in the paracetamol groups with first perceptible relief confirmed within 1 hour post dose [ Time Frame: 1 hour post dose ]
• Proportion of subjects in the paracetamol groups with first perceptible relief confirmed within 2 hours post dose [ Time Frame: 2 hours post dose ]
• Proportion of subjects in the paracetamol groups with meaningful relief at individual time points post dose [ Time Frame: Baseline to 6 hours post dose ]
• Change from baseline in SPRID (Sum of Pain Relief and Pain Intensity Differences) at individual time points post dose [ Time Frame: Baseline to 6 hours post dose ]
• Change from baseline in Total Pain Relief Score (TOTPAR) at individual time points post dose [ Time Frame: Baseline to 6 hours post dose ]
• Time to perceptible relief [ Time Frame: Baseline to 6 hours post dose ]
• Change from baseline Sum of Pain Intensity Differences (SPID) at individual time points [ Time Frame: Baseline to 6 hours post dose ]
• Time to rescue analgesic [ Time Frame: Baseline to 6 hours post dose ]
• Proportion of subjects taking rescue medication at individual time points post dose [ Time Frame: Baseline to 6 hours post dose ]
• Pain relief measured by a Verbal Categorized Scale at individual time points post dose [ Time Frame: Baseline to 6 hours post dose ]
• Pain intensity difference (PID) scores at individual time points post dose [ Time Frame: Baseline to 6 hours post dose ]
• Global evaluation of treatment experience based on a categorical scale at 6 hours post dose [ Time Frame: 6 hours post dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Post-operative Dental Pain Study Comparing Two Different Dosage of Analgesic Efficacy
• Official Title: A Study to Compare the Analgesic Efficacy of Two Different Paracetamol Doses as Measured by Post-operative Pain Relief
• Brief Summary: GlaxoSmithKline will be conducting this trial to compare analgesic efficacy of paracetamol 1000 mg vs 650 mg. The post-surgical dental pain model will be used to evaluate the analgesic efficacy of paracetamol. Each subject will be enrolled in the study for up to six weeks. The duration of the entire study will be approximately 18 weeks. Each subject will have to come to the clinic for three visits (Screening, Treatment and Follow up visits).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Post-surgical Dental Pain

Intervention

• Drug: Paracetamol 1000 mg
  Paracetamol 1000mg
• Drug: Paracetamol 650 mg
  Paracetamol 650 mg
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Paracetamol 1000mg
  Paracetamol 1000mg
  Intervention: Drug: Paracetamol 1000 mg
• Experimental: Paracetamol 650 mg
  Paracetamol 650 mg
  Intervention: Drug: Paracetamol 650 mg
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: Yue Y, Collaku A, Brown J, Buchanan WL, Reed K, Cooper SA, Otto J. Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies. Clin Ther. 2013 Sep;35(9):1306-20. doi: 10.1016/j.clinthera.2013.07.422. Epub 2013 Aug 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 27, 2015): 401
• Original Estimated Enrollment (submitted: February 23, 2010): 440
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects aged 18 to 45 years with moderate-to-severe dental pain as assessed by verbal rating scale (VRS) and confirmed by a score of at least 50 mm out of 100 mm using a visual analogue (VAS) following the surgical removal of up to two mandibular third molars. If only one mandibular third molar is removed, it must be a full bony impaction. If two mandibular third molars are removed, both may be partial bony impactions OR there may be a combination of one full bony impaction with the second tooth being erupted, soft tissue impaction, or partial bony impaction. Ipsilateral maxillary third molars may be removed at the surgeon's discretion, regardless of impaction level.

Exclusion Criteria:

• Pregnant and lactating females
• Allergy/intolerance to study materials or nitrous oxide or local anaesthetic used during surgery
• Current or recurrent liver, kidney or cardiac disease, stomach ulcers, gastrointestinal bleeding, gastroesophageal reflux disease, bronchospasm, rhinitis, urticaria or asthma

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01075243
• Other Study ID Numbers: A4000685
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Study Director, GSK
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: April 2015